There has been a continuing need for improved methods for the preparation of mineral compositions, especially calcium phosphate-containing minerals. This long-felt need is reflected in part by the great amount of research found in the pertinent literature. While such interest and need stems from a number of industrial interests, the desire to provide materials which closely mimic mammalian bone for use in repair and replacement of such bone has been a major motivating force. Such minerals are principally calcium phosphate apatites as found in teeth and bones. For example, type-B carbonated hydroxyapatite [Ca5(PO4)3-x(CO3)x(OH)] is the principal mineral phase found in the body, with variations in protein and organic content determining the ultimate composition, crystal size, morphology, and structure of the body portions formed therefrom.
Calcium phosphate ceramics have been fabricated and implanted in mammals in various forms including, but not limited to, shaped bodies and cements. Different stoichiometric compositions such as hydroxyapatite (HAp), tricalcium phosphate (TCP), tetracalcium phosphate (TTCP), and other calcium phosphate salts and minerals, have all been employed to this end in an attempt to match the adaptability, biocompatibility, structure, and strength of natural bone. The role of pore size and porosity in promoting revascularization, healing, and remodeling of bone is now recognized as a critical property for bone replacement materials. Despite tremendous efforts directed to the preparation of porous calcium phosphate materials for such uses, significant shortcomings still remain. This invention overcomes those shortcomings and describes porous calcium phosphate and a wide variety of other inorganic materials which, in the case of calcium phosphates, closely resemble bone, and methods for the fabrication of such materials as shaped bodies for biological, chemical, industrial, and many other applications.
Early ceramic biomaterials exhibited problems derived from chemical and processing shortcomings that limited stoichiometric control, crystal morphology, surface properties, and, ultimately, reactivity in the body. Intensive milling and comminution of natural minerals of varying composition was required, followed by powder blending and ceramic processing at high temperatures to synthesize new phases for use in vivo.
A number of patents have issued which relate to ceramic biomaterials and are incorporated herein by reference. Among these are U.S. Pat. No. 4,880,610, B. R. Constantz, “In situ calcium phosphate minerals—method and composition;” U.S. Pat. No. 5,047,031, B. R. Constantz, “In situ calcium phosphate minerals method;” U.S. Pat. No. 5,129,905, B. R. Constantz, “Method for in situ prepared calcium phosphate minerals;” U.S. Pat. No. 4,149,893, H. Aoki, et al, “Orthopaedic and dental implant ceramic composition and process for preparing same;” U.S. Pat. No. 4,612,053, W. E. Brown, et al, “Combinations of sparingly soluble calcium phosphates in slurries and pastes as mineralizers and cements;” U.S. Pat. No. 4,673,355, E. T. Farris, et al, “Solid calcium phosphate materials;” U.S. Pat. No. 4,849,193, J. W. Palmer, et al., “Process of preparing hydroxyapatite;” U.S. Pat. No. 4,897,250, M. Sumita, “Process for producing calcium phosphate;” U.S. Pat. No. 5,322,675, Y. Hakamatsuka, “Method of preparing calcium phosphate;” U.S. Pat. No. 5,338,356, M. Hirano, et al “Calcium phosphate granular cement and method for producing same;” U.S. Pat. No. 5,427,754, F. Nagata, et al., “Method for production of platelike hydroxyapatite;” U.S. Pat. No. 5,496,399, I. C. Ison, et al., “Storage stable calcium phosphate cements;” U.S. Pat. No. 5,522,893, L. C. Chow. et al., “Calcium phosphate hydroxyapatite precursor and methods for making and using same;” U.S. Pat. No. 5,545,254, L. C. Chow, et al., “Calcium phosphate hydroxyapatite precursor and methods for making and using same;” U.S. Pat. No. 3,679,360, B. Rubin, et al., “Process for the preparation of brushite crystals;” U.S. Pat. No. 5,525,148, L. C. Chow, et al., “Self-setting calcium phosphate cements and methods for preparing and using them;” U.S. Pat. No. 5,034,352, J. Vit, et al., “Calcium phosphate materials;” and U.S. Pat. No. 5,409,982, A. Imura, et al “Tetracalcium phosphate-based materials and process for their preparation.”
Several patents describe the preparation of porous inorganic or ceramic structures using polymeric foams impregnated with a slurry of preformed ceramic particles. These are incorporated herein by reference: U.S. Pat. No. 3,833,386, L. L. Wood, et al, “Method of preparing porous ceramic structures by firing a polyurethane foam that is impregnated with inorganic material;” U.S. Pat. No. 3,877,973, F. E. G. Ravault, “Treatment of permeable materials;” U.S. Pat. No. 3,907,579, F. E. G. Ravault, “Manufacture of porous ceramic materials;” and U.S. Pat. No. 4,004,933, F. E. G. Ravault, “Production of porous ceramic materials.” However, none of aforementioned art specifically describes the preparation of porous metal or calcium phosphates and none employs the methods of this invention.
The prior art also describes the use of solution impregnated-polymeric foams to produce porous ceramic articles and these are incorporated herein by reference: U.S. Pat. No. 3,090,094, K. Schwartzwalder, et al, “Method of making porous ceramic articles;” U.S. Pat. No. 4,328,034 C. N. Ferguson, “Foam Composition and Process;” U.S. Pat. No. 4,859,383, M. E. Dillon, “Process of Producing a Composite Macrostructure of Organic and Inorganic Materials;” U.S. Pat. No. 4,983,573, J. D. Bolt, et al, “Process for making 90° K superconductors by impregnating cellulosic article with precursor solution;” U.S. Pat. No. 5,219,829, G. Bauer, et al, “Process and apparatus for the preparation of pulverulent metal oxides for ceramic compositions;” GB 2,260,538, P. Gant, “Porous ceramics;” U.S. Pat. No. 5,296,261, J. Bouet, et al, “Method of manufacturing a sponge-type support for an electrode in an electrochemical cell;” U.S. Pat. No. 5,338,334, Y. S. Zhen, et al, “Process for preparing submicron/nanosize ceramic powders from precursors incorporated within a polymeric foam;” and S. J. Powell and J. R. G. Evans, “The structure of ceramic foams prepared from polyurethane-ceramic suspensions,” Materials & Manufacturing Processes, 10(4):757 (1995). The focus of this art is directed to the preparation of either metal or metal oxide foams and/or particles. None of the disclosures of these aforementioned references mentions in situ solid phase formation via redox precipitation reaction from homogeneous solution as a formative method.
The prior art also discloses certain methods for fabricating, inorganic shaped bodies using natural, organic objects. These fabrication methods, however, are not without drawbacks which include cracking upon drying the green body and/or upon firing. To alleviate these problems, the fabrication processes typically involve controlled temperature and pressure conditions to achieve the desired end product. In addition, prior fabrication methods may include the additional steps of extensive material preparation to achieve proper purity, particle size distribution and orientation, intermediate drying and radiation steps, and sintering at temperatures above the range desired for employment in the present invention. For example, U.S. Pat. No. 5,298,205 issued to Hayes et. al. entitled “Ceramic Filter Process”, incorporated herein by reference, discloses a method of fabricating a porous ceramic body from an organic sponge saturated in an aqueous slurry comprised of gluten and particulate ceramic material fired at a temperature range from 1,100° to 1,300° C. Hayes teaches that the saturated sponge must be dehydrated prior to firing via microwave radiation, and includes a pre-soak heating step, and a hot pressing step.
While improvements have been made in materials synthesis and ceramic processing technology leading to porous ceramics and ceramic biomaterials, improved preparative methods, and the final products these methods yield, are still greatly desired. Generation of controlled porosity in ceramic biomaterials generally, and in calcium phosphate materials in particular, is crucial to the effective in vitro and in vivo use of these synthetic materials for regenerating human cells and tissues. This invention provides both novel, porous calcium phosphate materials and methods for preparing them. Methods relating to calcium phosphate-containing biomaterials, which exhibit improved biological properties, are also greatly desired despite the great efforts of others to achieve such improvements.
Accordingly, it is a principal object of this invention to provide improved inorganic, porous, shaped bodies, especially those formed of calcium phosphate.
A further object of the invention is to provide methods for forming such materials with improved yields, lower processing temperatures, greater compositional flexibility, and better control of porosity.
Yet another object provides materials with micro-, meso-, and macroporosity, as well as the ability to generate shaped porous solids having improved uniformity, biological activity, catalytic activity, and other properties.
Another object is to provide porous materials which are useful in the repair and/or replacement of bone in orthopaedic and dental procedures.
An additional object is to prepare a multiplicity of high purity, complex shaped objects, formed at temperatures below those commonly used in traditional firing methods.
Further objects will become apparent from a review of the present specification.